This application addresses the broad Challenge Area (05) Comparative Effectiveness Research and specific Challenge Topic, 05-GM-101: Anesthesiology Clinical Pharmacology Sepsis Trauma, Burn, and Peri-operative Injury Wound Healing. Traumatic brain injury (TBI) management centers upon minimizing secondary brain injury primarily through reducing elevated intracranial pressure.1-4 Therapies to reduce cerebral edema and the discrepancy between cerebral oxygen delivery and consumption, such as osmotic diuresis, hyperosmolar therapies, barbiturate coma and hypothermia have had varying success. Decompressive craniotomy (DC) has been employed for refractory intracranial hypertension (ICH) for more than 50 years and has regained therapeutic interest during the past decade. However, treatment guidelines for traumatic brain injury (TBI) from German, European (European Brain Injury Consortium)1 North-American (Brain Trauma Foundation)4 and international (pediatric neurosurgery)2 medical societies consider DC only as last resort treatment strategy after failure of conservative therapy. Not surprisingly, DC has been viewed as a maneuver with little therapeutic benefit since it had traditionally been applied after failure of days of medical therapy when the degree of secondary brain injury had already reached an irreversible point. More recently, DC has been incorporated into intracranial pressure treatment algorithms at an earlier time point in centers with aggressive neurocritical care units with some encouraging results.5-11 Unfortunately, the majority of these trials lack appropriate controls for comparison and vary in the duration of time between injury and the DC which make it difficult to draw meaningful conclusions about DC efficacy. Given this important gap in clinical knowledge combined with the significant public health burden, and the magnitude of direct and societal cost of these injuries, the proposed research will have considerable impact in the delivery of care and outcomes for TBI patients. The invasive nature of DC and the significant expense of a randomized trial comparing DC to medical management make such a trial unfeasible. In the absence of a well designed, randomized trial other methods are required to define the role of DC in the management of TBI. This comparative effectiveness research proposal employs a propensity score analysis which creates balanced groups of patients and compares their survival according to whether or not they underwent DC. This proposal will solicit retrospective data from 10 Level One adult and pediatric trauma centers with the support of the American Association of the Surgery of Trauma and its Multi-Institutional Trials Committee. PUBLIC HEALTH RELEVANCE: Traumatic brain injury (TBI) is a serious public health problem in the United States with approximately 1.4 million people sustaining a traumatic brain injury annually.12 Of these, 50,000 die and 235,000 are hospitalized yearly leading to direct medical costs and costs as a result of lost productivity an estimated $60 billion in the United States in the year 2000.14 Identifying improved treatment strategies to manage patients with moderate to severe traumatic brain injury is necessary and would have tremendous public health impact.